Human CD4 mimicry by anti-idiotypic monoclonal antibody 16D7 is based on a conformational epitope

Immunology Letters
F PerosaF Dammacco

Abstract

The mouse anti-idiotypic mAb (mAb2) 16D7 recognizes the paratope (combining site-associated epitope) of the syngeneic anti-human CD4 mAb HP2/6 (mAb1), a down-modulator of T cell function. 16D7 mimics CD4 in xenogeneic settings in humans and can thus be used to target CD4+ T cells for therapeutic purposes. To define the minimum structural requirement for CD4 mimicry, 16D7 isolated L and H chains were tested for their ability to inhibit mAb1 binding to either CD4 Ag or to mAb2. 16D7 L only specifically inhibited these interactions. Alignment of 16D7 L variable region sequence with that of CD4 defined peptides L2, L3 and L7 with at least 68% of similarity and 30% of identity to exposed regions of CD4. Furthermore, peptides L1, L4, L5, L6 and L8 were selected from a set of 10-mer overlapping peptides (covering the FW and CDR regions of 16D7 L) because of their reactivity with mAb1. Only the synthesized L2 reacted with HP2/6 in slot dot assay and inhibited mAb2-mAb1 interaction. Immunization of BALB/c mice with 16D7, 16D7-F(ab')2, 16D7 L and L2, resulted in the production of CD4-specific Ab3 only in mice immunized with 16D7 and its F(ab')2 fragments. The lack of CD4 reactivity with sera elicited with 16D7 L and L2 was not due to the...Continue Reading

References

Feb 1, 1987·European Journal of Immunology·A C CarreraM O De Landazuri
Jan 1, 1994·International Journal of Clinical & Laboratory Research·F Perosa, F Dammacco
Oct 1, 1996·Proceedings of the Society for Experimental Biology and Medicine·C A Bona
Aug 26, 1998·Rheumatic Diseases Clinics of North America·F C Breedveld
Dec 4, 1998·Springer Seminars in Immunopathology·E H ChoyG S Panayi
Nov 9, 2000·European Journal of Immunology·L SpendloveL G Durrant
Nov 9, 2001·Clinical and Experimental Medicine·F PerosaF Dammacco
Jun 18, 2003·Current Opinion in Pharmacology·Peter C Taylor

❮ Previous
Next ❯

Citations

Nov 3, 2010·Journal of Molecular Recognition : JMR·Peter TimmermanDanièle Altschuh
Jan 30, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anat BurkovitzYanay Ofran

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.